This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term goal of this study is to understand the role of viral immune modulators for monkeypox virus (MPV) and cowpox virus (CPV) virulence. Individuals infected with MPV during the 2003 outbreak developed a strong MPV-specific T cell response, but the MPV-specific T cells were not stimulated by MPV-infected antigen presenting cells (APC) in vitro . In contrast, infection of APC by the vaccine strain Vaccinia-virus (VV) WR activated cross-reactive CD8+ and CD4+ T cells from MPV-infected individuals. These data strongly suggest that MPV prevents T cell stimulation by expressing immunomodulators that are absent in VV. Similarly, we observed that CPV-infected cells did not stimulate T cells. We succeeded in identifying the gene products of CPV that are responsible for T cell evasion. We are currently evaluating homologous genes in the MPV-genome for their ability to inhibit T cell stimulation.